We have identified three functionally distinct regions of the MuLV genome that distinguish leukemogenic and non-leukemogenic viral isolates. These include gp70 and p15E (plus R) coding segments and the LTR. We are now constructing site-specific recombinants by ligation of fragments derived from DNA clones of viruses that differ in leukemogenicity. The goal is to prepare viruses with different combinations of the three distinct coding segments and to test their disease inducing properties. We hope to be able to determine the role each genomic segment plays in determining the disease phenotype of the virus.